The long-term goal of the Breast Cancer (BC) Program is to elucidate the biology, genetics and biochemistry of breast cancer, and to apply this knowledge towards diagnostic, therapeutic and preventive strategies. To achieve this end, the following Specific Goals will be pursued: 1) To identify aberrant regulatory pathways in breast cancer pathogenesis. Specifically, by analyzing tumor biopsies and model systems, we will dissect the pathways responsible for distinct subtypes of breast cancer and elucidate their mechanistic role in tumor development. 2) To optimize the treatment and prevention of breast cancer. By using tissue, serum and imaging-based biomarkers, we will identify suitable patients for targeted therapy and then measure its efficacy. 3) To improve the quality of breast cancer care. By using novel methodologies to characterize the short and long term risks associated with standard breast cancer treatment, we will conduct clinical trials to evaluate novel interventions to diminish these effects. Since the prior grant period, the number of institution-based clinical trials in breast cancer and the number of patients accrued to therapeutic and supportive care trials has increased, with several investigators leading multi-center national and local trials. Over 12% of all patients, and 39% of eligible patients, are enrolled on trials. A noteworthy feature of the clinical research is minority accrual to clinical trials, with 58% of patients enrolled in trials identified as either African-American or Hispanic. The BC program consists of 29 members (16 full members, 12 clinical members, and 1 associate member) from fourteen departments within the College of Physicians &Surgeons, the Mailman School of Public Health and the College of Dental Medicine at Columbia University. The Program is supported by large program project grants, including a breast cancer NCI P01 focused on signaling pathways in breast cancer and a DoD Center of Excellence focused on disparities in breast cancer treatment. For the last budget year of the grant (July 1, 2006 - June 30, 2007), the BC Program received a total of $7.9M (direct costs) in cancer-relevant grant support, including $2.6M (direct costs) in NCI funding, $3.2M (direct costs) in other cancer-related peer-reviewed funding, and $2.1M (direct costs) in cancer-related non-peer-reviewed funding. The total number of publications since the previous submission (i.e., 2003- present) was 177, of which 18.6% were intra-programmatic and 40.7% % inter-programmatic.